Monthly Archives: August 2014

Is your home harming you? Asthma, allergies and indoor mould

It is hard to escape indoor mould. It is most commonly found in the wet areas of the home, especially the bathroom and the kitchen, but it can grow anywhere. We all agree that it’s unsightly, but the bigger…

Author

John Burgess

Research Fellow, CRE for Chronic Respiratory Disease, Centre for Epidemiology and Biostatistics at University of Melbourne

Disclosure Statement

John Burgess receives funding from NHMRC Australia through the Centre for Research Excellence in Chronic Resplratory Disease.

It is hard to escape indoor mould. It is most commonly found in the wet areas of the home, especially the bathroom and the kitchen, but it can grow anywhere. We all agree that it’s unsightly, but the bigger problem is it can harm your lungs.

According to the findings from our study published recently in the journal Respirology, indoor mould can increase the risk of active asthma, even in those who don’t have an allergy to mould.

The good news is that getting rid of the culprit may reduce the incidence of asthma.

Asthma in middle age

Our research involved the participants in the Tasmanian Longitudinal Health Study, the world’s largest and longest-running population-based study of lung health. This study started in 1968 when 8,583 seven-year-old Tasmanian school-children were enrolled by their parents.

Now in middle age, these original seven-year-olds have been followed at intervals, most recently in 2004-06. At that follow-up, we traced 5,729 participants to determine whether they had asthma or asthma-linked symptoms and the presence of visible mould and other airborne pollutants in their homes. We then allergy tested a subset of 1,383 participants.

When we analysed the data, we found the overall risk of active asthma was increased by 26% in those who had visible mould in the home in the last 12 months.

We also found that the more rooms in the house affected by mould, the greater the risk of active asthma. In other words, there was evidence that the “dose” of mould influenced the risk of active asthma.

These are novel findings, adding to the existing body of knowledge on what might cause asthma.

Identifying the cause

All asthma is not necessarily the same. A lot of asthma is “allergic”, developing in those who test positive to a skin test for a variety of possible allergens. This applies particularly to children and teenagers.

But asthma can also be “non-allergic”, developing in those with negative allergy skin tests. This type of asthma tends to occur more in adults, and interestingly, more often in women than men.

A considerable amount of asthma research has been done with children and adolescents, and in this age group, the risk for allergic asthma associated with mould sensitivity is well known.

Allergic asthma generally develops in childhood. KristyFaith

But not so well known is that mould exposure can be associated with non-allergic asthma, as our study showed. Our finding that this association was stronger in men than women was a little unexpected, and of considerable interest.

Much of the problem with mould lies with its ability to induce an allergic response in persons genetically predisposed – and mould allergy is common. In our study, 35% of participants reported mould in the home in the last 12 months and 13% of those skin tested had mould allergy. Other studies have found mould allergy in up to 24% of the general population and up to 80% among asthmatics.

One of the problems in trying to decide if mould has a causal role in asthma is that mould allergy often occurs in common with allergies to other asthma-related agents, particularly house dust mites. This co-existence makes it difficult to tease out the role of any single agent.

In addition, mould and dampness go hand in hand, and excessive indoor dampness in its own right is a known risk factor for asthma. Given the potential for climate change to lead to more extreme weather and increase the risk of flooding, indoor dampness may well become more of a problem in the future.

Allergic sensitisation is not the only mechanism by which mould can affect lung health. Mould produces various toxic and chemical substances including mycotoxins, beta-glucans, ergosterol and volatile organic compounds that can have a direct inflammatory effect on the lining of the airways. Such substances don’t depend on inducing an allergic response for their effect on the lungs.

To complicate matters further, how the lungs respond to such agents depends on the “dose” to which an individual is exposed and on the variability in the way different people respond to the same lung stressor.

Mould and dampness go hand in hand. Abby flat-coat/Flickr

Reducing the risk

Health authorities suggest that removing mould from the home can make a difference to people susceptible to asthma.

There are several treatments for mould, such as Tea Tree Oil and fermented vinegar solutions. It’s best avoid dry brushes (which can spread mould further) and bleach, which doesn’t kill mould (it merely bleaches the colour so it looks like it has disappeared).

It’s also important to address the causes of mould. This comes down to lessening indoor humidity and dampness by improving home ventilation and heating. This will be more difficult in older houses, which may have ongoing problems with dampness because or broken roof tiles, poor cavity wall ventilation and rising damp.

Finally, all asthma sufferers should routinely use their preventer and reliever medications as prescribed for asthma control and symptom relief.

Ingredients in chocolate, tea and berries could guard against diabetes

EurekAlert!, 01/20/2014

Eating high levels of flavonoids including anthocyanins and other compounds (found in berries, tea, and chocolate) could offer protection from type 2 diabetes – according to research from the University of East Anglia (UEA) and King’s College London. Findings published today in the Journal of Nutrition reveal that high intakes of these dietary compounds are associated with lower insulin resistance and better blood glucose regulation. A study of almost 2,000 people also found that these food groups lower inflammation which, when chronic, is associated with diabetes, obesity, cardiovascular disease, and cancer. Prof Aedin Cassidy from UEA’s Norwich Medical School led the research. She said: “Our research looked at the benefits of eating certain sub–groups of flavanoids. We focused on flavones, which are found in herbs and vegetables such as parsley, thyme, and celery, and anthocyanins, found in berries, red grapes, wine and other red or blue–coloured fruits and vegetables.

Herbal medicines warning: unregistered and unreliable

Monday, 24 February 2014

Researchers at the University of Adelaide have found that many so-called herbal medicines being sold in Australia are either not registered for sale or their contents differ to the legally registered items, prompting warnings about what consumers are buying.

A survey conducted by a team from the University’s School of Medical Sciences investigated 121 products all claiming to be herbal remedies for either arthritis, cold and flu, gastrointestinal problems, stress, or premenstrual syndrome.

The results, being published in next month’s Journal of Forensic and Legal Medicine, show that:
– 22 (or 18%) of the products were not registered with the Australian Register of Therapeutic Goods, despite this being a legal requirement of their sale
– 59 (or 60%) of the registered products had different ingredient concentrations listed on their websites compared with the Therapeutic Goods listings, making them non-compliant for sale
– Some of the remedies had substituted one ingredient for another.

The researchers also purchased sample items of 15 of these products over the counter at health food stores and pharmacies, and discovered that only two of them had ingredient concentrations that were consistent between the packaging, the information on their website, and their official Therapeutic Goods listing.

“More than two-thirds of the 121 products we surveyed were in some way not compliant for sale. That is a major concern for the community as well as for health professionals, with confusion about what is really contained in herbal medicines,” says a senior author of the study, University of Adelaide toxicologist Dr Ian Musgrave.

“In the scientific community there is a great deal of concern about herbal remedies and their interactions with prescription drugs, such as steroid drugs and the blood-thinning drug warfarin, to name just two common examples.

“Our survey reinforces that there is a lack of quality information about herbal remedies. This disparity of information is a concern, as purchasers may be exposed to potentially hazardous concentrations of materials, or be at higher risk of overdose.”

Co-author and University of Adelaide forensic pathologist Professor Byard AO says there are also implications for pathologists such as himself when trying to determine the cause of an individual’s death.

“Because of the lack of good quality information, it may not be possible to determine what herbal substance a person has been exposed to prior to death and in what concentration. This could further exacerbate the problem of determining what role herbal medicines may play in certain forensic cases,” Professor Byard says.

Surprising Information About Women And Heart Disease
Heart disease is the leading cause of death in men and women. Unfortunately, women are at a disadvantage when it comes to emphasizing their own cardiovascular health as they often don’t realize that heart disease is as much of a threat to them as it is to men. They are less likely than men to believe they’re having a heart attack and therefore are more likely to put off seeking treatment. In addition, doctors tend to treat women less aggressively with surgery, beta-blockers, ACE inhibitors or even aspirin after a heart attack.

Common symptoms of a heart attack shared by both genders include:

Chest discomfort

Arm discomfort

Shortness of breath

Sweating and clammy skin

Nausea

Stomach pain and feelings of indigestion

Additionally, women are more likely than men to experience unusual fatigue, sleep disturbances and anxiety, as well as throat, jaw and neck discomfort during a heart attack.

Don’t let your gender influence your response to heart concerns. If you experience these symptoms and feel you might be having a heart attack, don’t delay dialing 911 – the most effective window for treatment occurs during the first 60 minutes of symptoms.

Mammography has become a fighting word in recent years, with some researchers questioning its value and others staunchly defending it.

One especially disturbing criticism is that screening mammography may lead to “overtreatment,” in which some women go through grueling therapies — surgery, radiation, chemotherapy — that they do not need. Indeed, some studies estimate that 19 percent or more of women whose breast cancers are found by mammography wind up being overtreated.

Picture Your Life

We asked our readers to share insights from their experiences with breast cancer. Here are some of their stories.

This problem occurs, researchers say, because mammography can “overdiagnose” breast cancer, meaning that some of the tiny cancers it finds would probably never progress or threaten the patient’s life. But they are treated anyway.

So where are these overtreated women? Nobody knows.

They are out there somewhere, studies suggest. But the figures on overtreatment are based on theory and calculations, not on counting the heads of actual patients known to have experienced it. No one can point to a particular woman and say, “Here’s a patient who went through the wringer for nothing.”

Overdiagnosis is not the same as a false positive result, in which a test like a mammogram initially suggests a problem but is proved wrong. False positives are frightening and expensive, but overtreatment is the potential harm of mammography that worries doctors most, according to an article published last week in The Journal of the American Medical Association.

But the authors also say that estimates of how often overdiagnosis and overtreatment occur are among the least reliable and most controversial of all the data on mammography.

In the past, overdiagnosis was thought to apply mainly to ductal carcinoma in situ, or D.C.I.S., a breast growth that may or may not turn cancerous. Now, researchers think that invasive cancers are also being overdiagnosed and overtreated by mammography.

The concept of overtreatment is based on the belief that not all breast cancers are deadly. Some never progress, researchers suspect, and some progress so slowly that the patient will probably die of something else, particularly if she is older or has other health problems.

But mammography can find all of these tumors, even those too small to feel. And doctors and patients rarely watch and wait — once a tumor is found, it is treated, because nobody knows how to tell the dangerous ones from those that could be safely left alone.

“Everyone has an anecdote of a small spot on mammography year after year that was finally biopsied and turned out to be positive — invasive, low grade,” said Dr. Constance Lehman, a radiologist at the Fred Hutchinson Cancer Center and the director of breast imaging at the University of Washington in Seattle.

Where do the numerical estimates of overdiagnosis come from? In several large studies of mammography screening, women judged to have the same risk of breast cancer were picked at random to have the test or to skip it. Early on, more cancers were expected in the mammogram group, because the test can find small tumors.

Over time, the groups should have equalized, because if small tumors in the unscreened group were really life-threatening, they would have grown big enough to be felt or caused other symptoms.

But in several studies, the number of cancers in the unscreened group never caught up with the number in the mammography group. The reason for the difference, researchers assume, is that there must have been women in the unscreened group who had cancers that were never diagnosed and never progressed — and therefore did not need treatment.

The next step is to subtract the number of cancers in the unscreened group from the number in the mammography group. The result is the estimate of how many women in the mammography group were overtreated.

“We don’t know which individual women those were,” said Dr. Lydia E. Pace, of Brigham and Women’s Hospital, an author of the new paper. “All we know is the proportion, and a lot of people would argue that we don’t really know the proportion.”

This kind of calculation was used in a Canadian study of about 90,000 women, published in February in the journal BMJ. The authors found that after 15 years there was a “residual excess” of 106 invasive cancers in the mammography group. The authors attributed that to overdiagnosis, and said that it amounted to 22 percent of the 484 invasive cancers found by mammography. They concluded that for every 424 women who had mammography in the study, one was overdiagnosed.

Other studies have estimated overdiagnosis in different ways, with huge variations in the results, reporting that 5 percent to 50 percent of cancers found on mammograms are overdiagnosed. To make it clear that the numbers are uncertain, some offer ranges: For example, one says that if 10,000 50-year-old women have annual mammograms for 10 years, 30 to 137 women will be overdiagnosed.

It is frightening to consider the prospect that mammography could be leading some down a slippery slope to unneeded surgery, chemotherapy and radiation, with all their risks and side effects. But the numbers on overdiagnosis are all over the map, a shaky foundation on which to base important decisions.

The best hope for resolving the confusion may lie in molecular tests that can tell the difference between dangerous tumors and those unlikely to progress — but those tests are in the future.

Explainer: what is Alzheimer’s disease?

Alzheimer’s disease causes progressive damage to the brain, resulting in problems with memory, cognition, social engagement, and, ultimately, a person’s ability to care for themselves. Alzheimer’s is the…

The loss of life quality over the possible 15-year duration of Alzheimer’s is immeasurable, as is the burden placed on unpaid caregivers. Around 70% of people with Alzheimer’s will require supported or permanent residential care as their disease progresses.

Risk factors

The risk of Alzheimer’s increases with age; three in ten people over the age of 85 and almost one in ten people over 65 have some form of dementia.

Apart from age, lifestyle factors such as physical or mental inactivity, obesity, alcohol and cigarette smoking increase the risk of Alzheimer’s. Head injury with loss of consciousness may also play a role.

A small percentage of cases are a result of known genetic abnormalities that are most commonly associated with younger-onset Alzheimer’s, which is diagnosed between 30 and 65 years.

The symptoms are identical to those seen in people who present in their later years. But an accurate diagnosis can be difficult to obtain, with symptoms often attributed to stress or depression.

Symptoms and diagnosis

Subtle changes to memory, speech and language may initially only be evident to family members. Further changes in the ability to orientate in new surroundings, solve problems, plan and perform familiar tasks including money handling may be strong indicators of underlying degeneration.

The affected person may only have limited insight to the issues raised, and may be reluctant to seek medical attention.

To assist in an Alzheimer’s diagnosis, a neurologist will perform a behavioural assessment looking at reflexes, coordination, balance and gait, as well as eye movement, sensation and speech. The neurologist will be looking for signs of muscle weakness, fascinations and tremor, to rule out other confounding causes of illness.

You can expect to undergo some kind of brain imaging such as magnetic resonance imaging (MRI) or computed tomography (CT) scans to look for changes to the structure of the brain anatomy. Evidence of atrophy — spaces which indicate that brain cells have degenerated – can help confirm the diagnosis.

Sonographers who interpret the scans can detect structural changes in the cortical areas that control thinking, planning, memory and speech. They can also help to determine other possible causes of illness such as stroke or lesion that could affect cognition, movement or speech.

These tests are often administered 12 months apart (sometimes more frequently) to observe which areas of cognition the person is having the most difficulty with, and also the rate at which a person may be progressing.

Earliest detection of Alzheimer’s makes for the best outcome for life planning. Those affected may want to make specific medical directives and appoint someone to take care of their legal and financial matters. Many people decide to take trips and make memories; others join workshops that offer creative suggestions for dealing with the changes that may arise as the illness progresses.

Treatment and screening

Currently two classes of prescription medicine are available to treat the cognitive symptoms of Alzheimer’s after a diagnosis of clinical Alzheimer’s has been made.

But these drugs cannot cure or reverse the changes in the brain caused by the illness, so the most appropriate target for any therapeutic intervention is the early, prodromal phase of illness, where patients experience mild cognitive impairment.

The idea is to stop aggregations of the proteins Amyloid-β and Tau from depositing in brain regions, which eventually leads to Alzheimer’s.

Screening for these proteins in the research setting involves using fluorescence or brain amyloid imaging, and cerebrospinal fluid (CSF) analysis in persons considered to be at risk of progressing to symptomatic Alzheimer’s.

But these methods are expensive and invasive and not practicable for use in the community health-care setting, particularly in countries without a public health safety net.

Current research

Our research team is currently using blood tests to screen for genes associated with inherited Alzheimer’s. These tests can be used to confirm the cause of a familial illness or to predict whether a healthy person with a family history of illness is likely to progress to a disease state.

Blood tests are also a valuable tool for monitoring the biochemical, or altered physiological state of a person. Researchers are developing a blood test that could show evidence of brain changes and be used as a predictor of future cognitive decline. The test would need to be sensitive enough to measure markers of interest, with a high degree of specificity to ensure the findings are valid.

A research team in the United States, for instance, has successfully used a lipodemic approach to detect pre-clinical Alzheimer’s. They identified a set of ten lipids extracted from peripheral blood that could be used to accurately predict that otherwise healthy adults would develop early signs of Alzheimer’s within three years.

We are using a different approach, measuring the concentrations of specific isoforms of pathological Alzheimer’s proteins Amyloid-β and Tau in serum, plasma and saliva in an effort to accurately detect early evidence of disease. These are the same proteins that are measured during a spinal tap.

We’ve had some initial success with this method in yet-to-be-published research. But it must now be validated in a larger cohort. Continued research will indicate if this method is effective at detecting pre-symptomatic Alzheimer’s in the wider community.

We’re also investigating whether inflammatory markers may influence a person’s susceptibility to Alzheimer’s.

Future detection

Taking a blood test to discover that you may suffer Alzheimer’s in the future is not something that everyone will wish to do. But early detection is crucial for effective intervention.

It’s likely that current and future drug trials targeting Amyloid-β and Tau will be most effective as preventative measures, rather than a cure for Alzheimer’s. This is because once the brain begins to show atrophy, the cells cannot be regenerated.

Although a definitive, commercially available blood test for Alzheimer’s is some way off, there is good reason to believe that we will be able to better retain sufferers’ precious memories, cognition and independence with better treatments in the future – minimising the impact of Alzheimer’s on the community.

Explainer: what are autoimmune diseases?

Autoimmune diseases, which include a range of around 80 different illnesses from rheumatoid arthritis to type 1 diabetes and multiple sclerosis, occur when the immune system attacks the body. These diseases…

Authors

Steven Maltby

Post-doctoral Fellow in Immunology & Genetics at University of Newcastle

Vicki Maltby

Post-doctoral fellow at University of Newcastle

Disclosure Statement

Steven Maltby receives funding from The University of Newcastle and the Canadian Institutes of Health Research. He is affiliated with The University of Newcastle and the Hunter Medical Research Institute.

Vicki Maltby receives funding from Multiple Sclerosis Research Australia. She is affiliated with the University of Newcastle and the Hunter Medical Research Institute.

Autoimmune diseases, which include a range of around 80 different illnesses from rheumatoid arthritis to type 1 diabetes and multiple sclerosis, occur when the immune system attacks the body.

These diseases are fairly common, affecting around one in 20 people in Australia and New Zealand, but they’re often under-appreciated because although they lead to long-term debilitating disease, they’re rarely a primary cause of death.

The autoimmune response

The immune system protects the body by recognising and dealing with a wide range of infectious agents, including viruses, bacteria, fungi and parasites (collectively known as pathogens). It functions like an army, patrolling the body looking for pathogens, and either containing them or killing them before they can cause infection and illness.

In order to handle a broad range of pathogens, the immune system produces millions of individual cells with the capacity to detect different, randomly generated targets. Since the immune system has no way of knowing what pathogen it may encounter, this approach gives it the ability to detect a nearly limitless range of targets.

When an immune cell first encounters its target, it replicates, so a large number of cells are able to recognise that same target. This provides the immune system with enough cells to contain and kill that pathogen as well as a stockpile of cells that will recognise the target quickly in the future.

This is how vaccination works – the vaccine causes replication of immune cells that can target specific pathogens and protect from future infections.

One unfortunate side effect of producing cells that can recognise so many targets is that some cells will recognise targets within our own bodies. Under normal conditions, these cells are removed from the system, so they don’t attack.

But in some people – for reasons that remain poorly understood – these cells are not removed. The cells think they’re attacking a pathogen when they attack the body – and they cause autoimmune disease. Each autoimmune disease results from immune cells attacking a different target within the body.

Similar conditions, such as asthma and allergies, are often confused with autoimmune diseases. But they’re not considered to be autoimmune because they don’t result from immune cells attacking their own body. Rather, they’re caused by immune cells recognising and reacting to a target that doesn’t cause disease, such as pollen in allergic asthma or peanut protein in food allergies.

Treatments for autoimmune diseases

Current approaches to treating autoimmune disease control symptoms rather than cure. In most cases, treatments known as functional replacement therapies replace a function that’s lost during disease (such as insulin injections in type I diabetes).

These treatments are often combined with anti-inflammatory medications, which limit the amount of damage being caused by the immune response. Several more recent therapies also block specific components of the immune response.

Peanut allergy is not an autoimmune disease because it doesn’t result from immune cells attacking the body.GFAF Expo/Flickr, CC BY-NC-SA

In severe cases, medications that completely block immune responses are used to reduce disease symptoms. This is known as immunosuppression, and these medications require a delicate balancing act; while blocking the immune response may protect from autoimmune disease, this unfortunately leaves the individual open to severe infections.

Three common autoimmune diseases

There are many recognised autoimmune diseases and a growing list of illnesses not traditionally thought to be linked to the immune system, such as schizophrenia and narcolepsy, are now being recognised as having autoimmune components.

Here’s how three common autoimmune diseases work.

Approximately 10% to 15% diabetics have the autoimmune form of the disease, known as type 1 diabetes.

Formerly known as insulin-dependent or juvenile diabetes, this illness is caused when the immune system attacks the beta cells in the pancreas. The pancreas is a gland located behind the stomach and beta cells normally produce insulin (beta cells are still present in type 2 diabetes but no longer respond properly to the body’s demand for insulin).

Insulin regulates levels of sugar (glucose) in the body, ensuring you store and break it down properly. In the absence of insulin, the body starts to use fat as a substitute energy source, leading to a build-up of dangerous chemicals in the body which can cause a potentially fatal condition known as ketoacidosis.

Multiple sclerosis affects the nervous system. Nerve cells in the brain and spinal cord communicate signals throughout the body and are wrapped in a protective cover called myelin that allows these signals to travel quickly.

The immune system attacks and damages this covering in people with multiple sclerosis, interfering with signals and causing a wide variety of physical and mental symptoms. The body is unable to repair the damage, and symptoms generally get progressively worse.

The patterns of autoimmune attacks can differ between people resulting in slightly different forms of disease. Some people get steadily worse while others have many short attacks, with stable periods in between. Current medications can only slow disease progression and manage symptoms.

Arthritis is a term for a range of conditions that result in damage to the joints, causing swelling, pain, stiffness and decreased movement. While different forms of arthritis have different causes, rheumatoid arthritis results from an autoimmune response against targets within the joint.

In rheumatoid arthritis, immune cells attack the joint surface damaging the cartilage that normally coats the bone, leading to bone grinding directly on bone. This leads to permanent damage to the bone and tissues surrounding the joint, causing pain and decreasing mobility.

The number of autoimmune diseases is growing as we discover more and more illnesses have an underlying autoimmune component. Current therapies mainly aim to replace a lost function in patients, or to broadly block inflammation.

Only through an improved understanding of how autoimmune disease starts and how each disease develops will we be able to provide improved therapies and ultimately cure these diseases.

Risks and benefits of hormone therapy: has medical dogma now been overturned?

Abstract

Background

In an integrated overview of the benefits and risks of menopausal hormone therapy (HT), the Women’s Health Initiative (WHI) investigators have claimed that their ‘findings … do not support use of this therapy for chronic disease prevention’. In an accompanying editorial, it was claimed that ‘the WHI overturned medical dogma regarding menopausal [HT]’.

Objectives

To evaluate those claims.

Methods

Epidemiological criteria of causation were applied to the evidence.

Results

A ‘global index’ purporting to summarize the overall benefit versus the risk of HT was not valid, and it was biased. For coronary heart disease, an increased risk in users of estrogen plus progestogen (E + P), previously reported by the WHI, was not confirmed.

The WHI study did not establish that E+ P increases the risk of breast cancer; the findings suggest that unopposed estrogen therapy (ET) does not increase the risk, and may even reduce it.

The findings for stroke and pulmonary embolism were compatible with an increased risk, and among E+ P users there werecredible reductions in the risk of colorectal and endometrial cancer. For E+ P and ET users, there were credible reductions in the risk of hip fracture. Under ‘worst case’ and ‘best case’ assumptions, the changes in the incidence of the outcomes attributable to HT were minor.

Conclusions

Over-interpretation and misrepresentation of the WHI findings have damaged the health and well-being of menopausal women by convincing them and their health professionals that the risks of HT outweigh the benefits.

A Surgical Procedure’s Risks, Unmentioned

Many patients assume that, like prescription drugs, surgical procedures and instruments undergo extensive testing and must be government-approved. It’s not necessarily so.

Developers, of course, do test new instruments, and practitioners often train with an expert before using them unsupervised to treat patients. And the Food and Drug Administration must confirm an instrument’s safety and effectiveness before it can be marketed — but only if the device is deemed significantly different from others already approved.

Surgical techniques, however, are not subject to the stringent approval process that drugs go through. And as with drugs, problems with new procedures may not become apparent until after they have been used many hundreds or thousands of times.

Such is the case with a popular treatment for a very common medical problem: uterine fibroids. The technique, called electric or power morcellation, has widespread appeal for both surgeons and patients. It is used during laparoscopic or robotic-assisted operations that are fast and effective, require only a tiny incision or none at all, and involve less pain, a shorter hospital stay and a quicker recovery. In most cases, these operations are safer than traditional surgery.

As recent reports have shown, however, power morcellation can also cause serious and sometimes life-threatening complications. Experts say that prospective patients are often not told about these risks before consenting to the operation.

The technique involves insertion of a tiny instrument with a rapidly rotating blade, the morcellator, that breaks up the fibroid so that it can be sucked out through the small opening of a laparoscope. But problems can arise months or years later if pieces of tissue escape into the pelvic cavity and seed themselves on other organs.

This problem is all the more serious if the fibroid that was morcellated happens to have contained a hidden cancer. Although the overwhelming majority of fibroids are benign, there is no certain way to tell before their removal if they harbor a cancer, which happens in 1 in 400 to 1 in 1,000 cases.

One such case involves a 41-year-old Bostonian, Dr. Amy J. Reed, an anesthesiologist and a mother of six, who now has a Stage 4 leiomyosarcoma after undergoing uterine morcellation. It is a rare but particularly aggressive uterine cancer. Dr. Reed and her husband, Dr. Hooman Noorchashm, a cardiothoracic surgeon, are waging a campaign through Change.org to halt use of the technique.

Despite several preoperative tests, neither Dr. Reed nor her surgeon suspected that cancer lurked within the fibroids that were removed. If she had had a traditional operation in which the fibroids were cut out or the entire uterus removed intact, it is highly unlikely that the cancer would have spread.

From 1983 through 2010, 13 unexpected uterine sarcomas were reported after uterine surgery on 5,666 patients. Among 1,192 women who underwent morcellation, two developed sarcoma that spread within the abdomen.

After reviewing the medical records of more than 1,000 women who received morcellation for fibroids, specialists at Brigham & Women’s Hospital in Boston found a ninefold higher rate of unexpected sarcoma than is now quoted to patients considering the procedure.

“These data suggest uterine morcellation carries a risk of disseminating unexpected malignancy with apparent associated risk of mortality much higher than appreciated currently,” the researchers wrote in the journal PLOS One in 2012.

Even benign uterine tissue, when it is spread to other parts of the abdomen during morcellation, can grow in places it doesn’t belong and cause pain, infection or bowel obstruction.

There is a technique that could make morcellation safer: encasing the tissue to be removed in a bag before it is broken up. But thus far, the procedure is infrequently used, and few surgeons are skilled in the technique.

Other established ways to treat bothersome fibroids are free of this potential risk, though complications like wound infection are possible.

Fibroids are extremely common, affecting half or more women during their reproductive years, when hormones foster their growth. They develop from the smooth muscle tissue of the uterus, ranging in size from tiny to huge, and often shrink after pregnancy and menopause.

Most women with fibroids are unaware they have them, but others can experience symptoms like prolonged heavy periods, bleeding between periods, pelvic pressure, constipation, frequent urination, backaches and anemia. They can sometimes cause infertility or miscarriage.

Fibroids are typically detected through a pelvic exam, sonogram or M.R.I., sometimes with saline solution or a dye used to better define their size and location.

Nothing needs to be done about a fibroid that causes no distress. Large, bothersome fibroids can often be shrunk by several months of treatment with medications that block estrogen and progesterone, causing temporary menopause and its attendant symptoms.

The drug mifepristone (RU-486) also can shrink fibroids, and Evista may do likewise, but only in postmenopausal women. Sometimes a low-dose oral contraceptive is used to reduce bleeding caused by fibroids without shrinking their size.

Noninvasive ultrasound surgery under M.R.I. guidance can be used to heat and destroy a fibroid without damaging the uterus. A fibroid also can be destroyed by injecting small particles into uterine arteries to cut off its blood supply.

Fibroids can be removed laparoscopically or robotically without damaging the uterus. If the fibroid is contained within the uterus, it can often be removed with surgical instruments inserted through the vagina and cervix. Some fibroids may be destroyed by applying heat or electric current to the uterine lining.

Very large, multiple or deep fibroids may require more traditional surgery, called an abdominal myomectomy, that spares the uterus, or with a hysterectomy, a more serious operation involving removal of the entire uterus, ending a woman’s menstrual periods and ability to bear children.

If you are contemplating treatment for symptomatic fibroids, your doctor should answer several important questions before you choose a method:

What is the nature of the problem, and how necessary is it to treat it?

What procedures are known to be effective, and what are the risks and benefits of each?

What is the approach you recommend, and how much experience do you have with it?

What are its possible complications, and how often do they occur?

Without a clear understanding of treatment options, their potential hazards as well as their effectiveness, it is not possible to for you to give informed consent.

What is gene therapy?

Every now and again you might read about gene therapy and efforts to correct serious genetic diseases. But I’m betting that very few readers have had gene therapy, nor have they ever met anyone who has, nor will they ever meet that many. The reasons are simple – while these procedures are possible in…

Author

Dean of Science and Professor of Molecular Biology at University of New South Wales

Disclosure Statement

Merlin Crossley works for the University of New South Wales. He receives research funding from the National Health and Medical Research Council and the Australian Research Council

It’s hard to replace plain flour with self-raising flour in a cake, but luckily, our chromosomes are more like cars. juni xu

Every now and again you might read about gene therapy and efforts to correct serious genetic diseases. But I’m betting that very few readers have had gene therapy, nor have they ever met anyone who has, nor will they ever meet that many.

The reasons are simple – while these procedures are possible in theory, in practice, it has proved remarkably difficult to insert new genetic materials into human patients and ensure that the new genes are sustainably expressed.

The difficulties encountered highlight the fact that we do not yet have enough fundamental knowledge about gene transfer and control. And what’s more, gene therapy is hugely expensive.

Why is gene therapy so hard?

Some things are easy to fix and others are not – it really depends on how things are constructed.

Machines, such as cars, are made from individual components – defective parts can be replaced by new parts. Similarly, if your house has a hole in the roof or a crack in the wall, it can be fixed by carving out the bad section and replacing it. This may be expensive, but it is possible.

On the other hand, if you bake a cake and use plain flour rather than self-raising flour, it is very hard to fix the problem later on.

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Living organisms are complicated – some parts, such as the brain, are a bit like cakes, but other components, such as blood cells, can be transplanted.

Several early efforts at gene therapy have focused on diseases of the blood, inherited anaemia, immune deficiencies, and blood clotting disorders. In these cases, the theory is relatively simple. But, in practice, gene therapy has proved much harder than we might have expected.

Theory and practice of human genetic modification

The first inherited diseases were described about a hundred years ago. At that time we barely understood what a gene was. About 70 years ago, DNA was identified as the genetic material.

In 1953, the structure of DNA was described by molecular biologists James Watson and Francis Crick and, shortly after that, we understood how genes encoded functional proteins.

For instance, the globin gene region encodes the oxygen-carrying protein haemoglobin. Patients with blood disorders, such as sickle cell anaemia, have a mutation in the gene encoding haemoglobin. The red blood cells in these patients become sticky and misshapen under certain conditions.

So the idea of gene therapy was born. Now that we understood the problem, could we provide the patient with a new, intact copy of a normal globin gene? Could they use the new gene to produce a normal haemoglobin protein?

To achieve this we had to get the gene into the patient’s body.

So how do you get genes in?

One can’t just bathe someone in a solution of DNA and expect the gene to get in, any more than one can submerge a computer in a tub of ticker tape computer code and expect it to take up the programs.

Computers are made so that there are portals available through which information can be inserted.

Living organisms, on the other hand, tend to guard themselves against foreign matter, and particularly against foreign DNA. This is because foreign DNA, in the form of viruses, is very dangerous indeed. Viruses are basically nothing but tiny packages of selfish DNA.

What’s more, we don’t just want to get the DNA in – we want it to get into the right cells. Our red blood cells do not last long since they are quickly worn out by being buffeted around our blood vessels – and they do not carry DNA anyway.

Normal red blood cells and a sickled blood cell. wellcome images

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If one wants to correct a defect in red blood cells, one strategy is to correct the defect in blood stem cells, then all the blood cells that descend from those cells will be corrected. This is one reason why research on stem cells is so important.

There are a number of ways to insert new genes into stem cells, such as:

micro-injection

zapping the cells with electricity so DNA can enter through holes blasted in the cell membrane

inserting DNA into viral-like lipid bubbles that fuse with the cell membrane

inserting the new DNA into an actual virus and utilising its expertise – evolved over millions of years – to penetrate and deliver genetic material into the cell.

In this last case, the DNA within the virus is wholly or largely deleted and the gene of interest inserted in its place. One virus – adeno-associated virus (AAV) – is proving to be particularly effective.

Interestingly, once the DNA gets into our cells, it does tend to be stitched into our chromosomes. It is as if the cell thinks a piece of our DNA has become detached and the “DNA repair machinery” wires it back in.

But getting new genes into enough cells on a scale that is sufficient to restore capacity to a whole human being is a major undertaking – so it is very expensive.

Epigenetic gene silencing

And there is another problem – over time foreign genes tend to get shut down.

Our cells have a highly sophisticated “anti-viral” software. We do not fully understand how the recognition and shut-down occurs but it certainly involves what are known as epigenetic silencing mechanisms.

Basically, once new DNA is recognised as foreign, it is covered by methyl groups that then lead to it being coiled up safely and packaged away in a fashion that is analogous to the quarantining of computer viruses. It is not actually removed, but it is silenced.

Should we be hopeful for future progress?

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Yes. There have been some notable successes. A patient with a form of inherited anaemia has received stem cells with a new gene and several haemophilia patients have benefited from a getting a new clotting factor gene.

More than 40 children with severe immune deficiency – so called “bubble kids” who might once have lived within plastic bubbles cut off from germs – have benefited from receiving new genes that are critical to white blood cells.

In the early trials, some patients developed a form of leukaemia when the new gene inserted and activated a neighbouring blood growth control gene, but later trials appear to be going well.

Then there is what some are calling the world’s most expensive drug – alipogene tiparvovec (trademarked name Glybera). In this case, an adeno-associated virus vector delivers a new lipoprotein lipase gene to patients who have inherited a deficiency in this gene and are likely to develop severe pancreatitis.

So gene therapy still offers hope. It remains good in theory, but challenging in practice. One hopes that as we understand better how to purify and grow stem cells, how to insert DNA efficiently, and how to overcome epigenetic silencing it will become cheaper, more effective and more diseases will become treatable.

But, in the immediate future, the number of treatments and people treated will be small – even when the condition is life-threatening and the need is extreme.

The related idea of genetic enhancement – the alteration of our genomes to improve cosmetic attributes or even sporting performance – attracts even more attention than gene therapy, but it is even more unlikely to become a widespread reality any time soon.